Intranasal antihistamines and corticosteroids in allergic rhinitis: A systematic review and meta-analysis.

BACKGROUND: There is insufficient systematized evidence on the effectiveness of individual intranasal medications in allergic rhinitis (AR). OBJECTIVES: We sought to perform a systematic review to compare the efficacy of individual intranasal corticosteroids and antihistamines against placebo in improving the nasal and ocular symptoms and the rhinoconjunctivitis-related quality of life of patients with perennial or seasonal AR. METHODS: The investigators searched 4 electronic bibliographic databases and 3 clinical trials databases for randomized controlled trials (1) assessing adult patients with seasonal or perennial AR and (2) comparing the use of intranasal corticosteroids or antihistamines versus placebo. Assessed outcomes included the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. The investigators performed random-effects meta-analyses of mean differences for each medication and outcome. The investigators assessed evidence certainty using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach. RESULTS: This review included 151 primary studies, most of which assessed patients with seasonal AR and displayed unclear or high risk of bias. Both in perennial and seasonal AR, most assessed treatments were more effective than placebo. In seasonal AR, azelastine-fluticasone, fluticasone furoate, and fluticasone propionate were the medications with the highest probability of resulting in moderate or large improvements in the Total Nasal Symptom Score and Rhinoconjunctivitis Quality-of-Life Questionnaire. Azelastine-fluticasone displayed the highest probability of resulting in moderate or large improvements of Total Ocular Symptom Score. Overall, evidence certainty was considered "high" in 6 of 46 analyses, "moderate" in 23 of 46 analyses, and "low"/"very low" in 17 of 46 analyses. CONCLUSIONS: Most intranasal medications are effective in improving rhinitis symptoms and quality of life. However, there are relevant differences in the associated evidence certainty.

HLA and Delayed Drug-Induced Hypersensitivity.

Delayed drug allergy reactions (DDAR) are potentially fatal. Certain human leukocyte antigen (HLA) alleles have been associated with delayed allergy reactions following the administration of particular drugs. Examples are HLA-B*57:01 (abacavir), HLA-B*15:02/HLA-A*31:01 (carbamazepine), and HLA-B*58:01 (allopurinol). Based on the identification of these associations, it may now be possible to prevent certain allergy reactions that were, until recently, considered unpredictable. In this review, we will focus on the pharmacogenetics of the best-studied associations between specific HLA alleles and delayed allergy reactions and describe the pathogenesis models proposed so far. Finally, we will evaluate the genetic screening strategies available and discuss the clinical relevance of a better understanding of the immunogenetics and mechanisms involved in DDAR.

Protocol for the systematic reviews on the desirable and undesirable effects of pharmacological treatments of allergic rhinitis informing the ARIA 2024 guidelines.

There is insufficient evidence regarding the comparative efficacy and safety of pharmacological treatments of allergic rhinitis (AR). In the context of informing the 2024 revision of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines, we plan to perform three systematic reviews of randomized controlled trials (RCTs) comparing the desirable and undesirable effects (i) between intranasal and oral medications for AR; (ii) between combinations of intranasal and oral medications versus nasal or oral medications alone; and (iii) among different intranasal specific medications. We will search four electronic bibliographic databases and three clinical trials databases for RCTs examining patients ≥ 12 years old with seasonal or perennial AR. Assessed outcomes will include the Total Nasal Symptom Score, the Total Ocular Symptom Score, and the Rhinoconjunctivitis Quality-of-Life Questionnaire. We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. If appropriate, we will perform a pairwise random-effects meta-analysis for each pair of assessed medication classes and outcomes, as well as a network meta-analysis to assess the comparative efficacy of intranasal medications among each other. Heterogeneity will be explored by sensitivity and subgroup analyses. This set of systematic reviews will allow for a comprehensive assessment of the effectiveness and safety of pharmacological interventions for AR and inform recommendations in the context of the ARIA guidelines.

Intranasal antihistamines and corticosteroids in the treatment of allergic rhinitis: a systematic review and meta-analysis protocol.

INTRODUCTION: Intranasal antihistamines and corticosteroids are some of the most frequently used drug classes in the treatment of allergic rhinitis. However, there is uncertainty as to whether effectiveness differences may exist among different intranasal specific medications. This systematic review aims to analyse and synthesise all evidence from randomised controlled trials (RCTs) on the effectiveness of intranasal antihistamines and corticosteroids in rhinitis nasal and ocular symptoms and in rhinoconjunctivitis-related quality-of-life. METHODS AND ANALYSIS: We will search four electronic bibliographic databases and three clinical trials databases for RCTs (1) assessing patients ≥12 years old with seasonal or perennial allergic rhinitis and (2) comparing the use of intranasal antihistamines or corticosteroids versus placebo. Assessed outcomes will include the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS) and the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. Certainty in the body of evidence for the analysed outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We will perform a random-effects meta-analysis for each assessed medication and outcome, presenting results as pooled mean differences and standardised mean differences. Heterogeneity will be explored by sensitivity and subgroup analyses, considering (1) the risk of bias, (2) the follow-up period and (3) the drug dose. ETHICS AND DISSEMINATION: Ethical considerations will not be required. Results will be disseminated in a peer-review journal. PROSPERO REGISTRATION NUMBER: CRD42023416573.